The interactions among non-coding RNA (ncRNA) and RNA binding protein (RBP) are increasingly recognized as one of basic mechanisms in gene regulation, and play a crucial role in cancer progressions. However, the current understanding of this regulation network, especially its dynamic spectrum according to the differentially expressed nodes (i.e. ncRNAs and RBP) is limited. Utilizing transcriptomics and interactomics resources, dysregulated RBP-ncRNA circuits (RNCs) are systematically dissected across 14 tumor types. We found these aberrant RNCs are robust and enriched with cancer-associated ncRNAs, RBPs and drug targets. Notably, the nodes in altered RNCs can jointly predict the clinical outcome while the individual node can’t, underscoring RNCs can serve as prognostic biomarkers. We identified 30 pan-cancer RNCs dysregulated at least in six tumor types. Pan-cancer RNC analysis can reveal novel mechanism of action (MOA) and repurpose for existing drugs. Importantly, our experiments elucidated the novel role of hsa-miR-224-5p, a member of the pan-cancer RNC hsa-miR-224-5p_MAGI2-AS3_MBNL2, in EMT program. Our analysis highlights the potential utilities of RNCs in elucidating ncRNA function in cancer, associating with clinical outcomes and discovering novel drug targets or MOA.

非编码 RNA (ncRNA) 和 RNA 结合蛋白 (RBP) 之间的相互作用越来越被认为是基因调控的基本机制之一，并且在癌症进展中起着至关重要的作用。然而，目前对该调节网络的理解，尤其是其根据差异表达节点（即ncRNA 和 RBP）是有限的。利用转录组学和相互作用组学资源，系统地剖析了 14 种肿瘤类型中失调的 RBP-ncRNA 回路（RNC）。我们发现这些异常的 RNC 很强大，并且富含与癌症相关的 ncRNA、RBP 和药物靶点。值得注意的是，改变的 RNC 中的节点可以共同预测临床结果，而单个节点则不能，强调 RNC 可以作为预后生物标志物。我们确定了至少在六种肿瘤类型中失调的 30 个泛癌 RNC。泛癌 RNC 分析可以揭示新的作用机制 (MOA) 并重新利用现有药物。重要的是，我们的实验阐明了 hsa-miR-224-5p（泛癌 RNC hsa-miR-224-5p_MAGI2-AS3_MBNL2 的成员）在 EMT 程序中的新作用。